Presentation title – In vivo Carcinogenicity studies.pptx

Introduction
Principle of the test
Description of method
Procedure
References

1. Presentation title – In vivo Carcinogenicity studies . Presented by : Submitted to : Neha Dr. saumya Das M. Pharm Associate Professor 2 nd semester NIET ( Pharmacy Institute) NOIDA INSTITUTE OF ENGINEERING AND TECHNOLOGY (PHARMACY INSTITUTE)

2. Table of Content Introduction Principle of the test Description of method Procedure References 20XX Sample Footer Text 2

3. Introduction • The original Test Guidelines 451 on Carcinogenicity was adopted in 1981 . • The updating of TG 451 has been carried out in parallel with revisions of TG 452 , Chronic Toxicity Studies , and 453 , Combined Chronic Toxicity / Carcinogenicity Studies . • This TG is designed to be used in the testing of a broad range of chemicals , including pesticides and industrial chemicals . • Most of these studies are carried out in rodents so these TG are designed primarily in those prospects . • For non – rodent species , the principles and procedures are outlined in this Guideline together with those outlined in OECD TG 409 , Repeated Dose 90 – day Oral toxicity study . 20XX Sample Footer Text 3

4. Cont….. The objectives of carcinogenicity studies covered by this test guideline include : - The identification of the carcinogenic properties of a chemical , resulting in an increased incidence of neoplasms , increased proportion of malignant neoplasms or a reduction in the time to appearance of neoplasms , compared with concurrent control groups. The identification of target organ ( s ) of carcinogenicity The identification of the time to appearance of neoplasms Characterization of the tumor dose – response relationship Identification of a no-observed-adverse-effect level ( NOAEL ) or point -Identification of a no – observed – adverse – effect of departure for establishment of a Benchmark Dose ( BMD ) Extrapolation of carcinogenic effects to low dose human exposure levels Provision of data to test hypotheses regarding mode of action

5. Principle of the test : • The test chemical is administered daily in graduated doses to several groups of test animals normally by oral route or by dermal or inhalation route . • The animals were observed closely for signs of toxicity and for the development of neoplastic lesions . • The animals may die during test process and are necropsied , and the surviving animals were and necropsied .

6. Description of method : Selection of animal species : - rodents ( eg - . , rat and mice ) Housing and feeding : - animals may be housed individually or be caged in small groups of same sex Temperature- 22 ° C ( ± 3 ° C ) - Relative humidity- 50-60 % -Lighting- 12hrs light and 12hrs dark -Feed- diet as per guidelines and drinking water is supplied . 3. Preparation of animals – healthy animals which are not involved in previous experiments, and which are acclimated for laboratory conditions has to choose . The weight variation for each sex of animal used should be minimal and not exceed ± 20 % of the mean weight .

7. Procedure : Number and sex of animals : each dose group and control group may contain 50 animals of each sex . Provision for interim kills and satellite groups : during test study there is a chance that animals may die due to development of neoplasms ( like 10 animals per sex ) , so to increase the statistical data accuracy animals will be added ( minimum of 5 animals per sex ) . Dose groups and Dosage : Atleast three dose levels and concurrent control should be used . Dose levels should be choosen based on shorter – term repeated dose study or range findings study . The data related to toxicological and toxicokinetic information is taken into consideration . Preparation of doses and administration of test substances : usually test substance is administered via oral route of administration but based of type of study route of administration will be varie . The test substance is dissolved in suitable vehicle and administer to the test group in diet or drinking water or gavage while control group is treated with only vehicle . For substances administered via diet or drinking water in long term toxicity studies the concentration of chemical substance should not exceed 5 % of the total diet. In case of oral administration the test substance is given daily for 7days per week for a period of 24 months , and in case of dermal administration test group is treated for 6hrs per day for a period of 24 months , and in inhalation route the test group is exposed for 6hrs daily for a period of 24 months .

8. Cont….. Duration of study : normally for rodents' duration is 24 months for some strains of mice 18 months will be sufficient ( e.g . , AKR / J , C3H / J , C57BL / 6J ) . Termination of study should be considered when the number of survivors in the lower dose group or control group falls below 25 % . In the case where only the higher dose group dies prematurely due to toxicity , this should not trigger the termination of study . Survival of each sex should be counted separately . The study should not be extended beyond the point when the data available from the study are no longer sufficient to enable a statistically valid evaluation to be made .

9. Observations : all animals should be tested for mortality or morbidity , toxicity , tumor growth and its location etc. Body weight should be tested at least once in a week for the first 13 weeks then once a month for next weeks . Food and water consumption should be measured once in a week for the first 13 weeks and then once in a month for next weeks . Analysis of blood samples and urine samples has to be done . Gross necropsy has to be done for test and control groups for careful observations of surface of body , all orifices , the cranial , thoracic and abdominal cavities and their contents . Histopathology of all tissues from higher dose and control groups , all tissues of animals dying or killed during study has to be done .

10. Cont….. Data and reporting : all data regarding toxicity , onset of tumor development , death or humane kill , signs of symptoms of all animals should be included . Test report should include the following information : Test chemical : - physical nature , purity , and physicochemical properties ; - identification data source of substance batch number certificate of chemical analysis Vehicle ( if appropriate ) : -justification for choice of vehicle ( if other than water ) ; Test animals : species / strain used and justification for choice made number , age , and sex of animals at start of test source , housing conditions , diet , etc . individual weights of animals at the start of the test ; 4. Test conditions : - rationale for route of administration and dose selection

11. Cont…. When applicable , the statistical methods used to analyze the data ; B details of test chemical formulation / diet preparation . analytical data on achieved concentration , stability and homogeneity of the preparation ; - route of administration and details of the administration of the test chemical ; for inhalation studies , whether nose only or whole body actual doses ( mg / kg body weight / day ) , and conversion factor from diet / drinking water test chemical concentration ( mg / kg or ppm ) to the actual dose , if applicable details of food and water quality ;

12. References : OECD ( 1995 ) , Report of the Consultation Meeting on Sub – chronic and Chronic Toxicity / Carcinogenicity Testing ( Rome , 1995 ) , internal working document , Environment Directorate , OECD , Paris . EPA ( 2005 ) . Guidelines for Carcinogen Risk Assessment Forum U.S. Environmental Protection Agency Washington , DC . OECD ( 2009 ) , Draft Guidance Document on the Design and Conduct of Chronic Toxicity and Carcinogenicity Studies , Series on Testing and Assessment No. 116 .

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